Transgenic animals are a valued tool in the arsenal of techniques employed in the elucidation of human disorders as well as in the characterization of the in vivo effects of a given therapeutic regimen. Such animals are characterized by the presence of a new or altered exogenous DNA integrated into their genome; usually to introduce a foreign gene and/or “knock out” an endogenous gene. To date, there are no known genetic or transgenic models for depression.
Major depression represents one of the most common mental illnesses, affecting between 5-10% of the population. The disease is characterized by extreme changes in mood which may also be associated with psychoses. Depression comes in varied forms and is an extremely difficult disorder to treat. Patients are often reluctant to seek the medical attention necessary to diagnose the disorder. Furthermore, even if patients do seek psychiatric help, psychoanalytic approaches alone are often ineffective at providing amelioration for the disorder.
Clinically, depression may be classified into depressive disorder, dysthymic disorder and depressive disorder not otherwise specified. Major depressive disorder and dysthymic disorder are differentiated based on chronicity, severity and persistence. In major depression, the mood must be present for two weeks. In dysthymic disorder, the depressed mood must be present most days over a period of two years. Usually major depressive disorder is characterized by its sharp contrast to normal functioning. A person with major depressive episode can be functioning normally and feeling fine and suddenly develops severe symptoms of depression. By contrast, a person with dysthymic disorder has chronic depression with less severe symptoms than major depression.
Numerous drugs have been developed to treat depression including for example serotonin re-uptake inhibitors (SSRI), such as sertraline (registered trademark ZOLOFT, Pfizer), fluoxetine (PROZAC—Eli Lilly), paroxetine (PAXIL—Smith Kline Beecham) and fluvoxamine (LWOX); tricyclic antidepressants such as ELAVIL (Merck, Sharpe and Dohme), aminoketone antidepressants such as bupropion, and lithium, a metal used to treat bipolar disorder. However, these drugs are very potent, often generating problematic side effects such as lethargy, clouded thinking and a lack of ability to concentrate. Further, the road to development of such drugs is long and expensive and hindered by the lack of availability of suitable animal models on which new antidepressant drugs can be tested.
Insights into the monitoring and management of depressive disorders are needed in order to provide more effective treatment for the complex array of disorders that fall under the term “depression”. However, the precise identification of models which may be employed to study such disorders remains elusive. In order to develop pharmacologic strategies for treatment of depression in humans, it will be important to establish animal models which accurately reflect the pathological profile of the disorders.